Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuroblastoma is one of the most common malignant neoplasms in infants and children under 5 years of age. The commonest manifestations are abdominal masses or metastases. The case reported showed unusual manifestations as the presenting features simulated myasthenia gravis in all aspects. He was a child, aged 3 years, who was admitted because of generalized weakness, inability to open his eyes and lethargy. Radiography showed an oval opacity at the right upper zone of the chest. A thorocotomy was performed and a tumour was removed from the posterior mediastinum. Histopathology confirmed diagnosis of ganglioneuroblastoma. There is only one similar report in the medical literature.
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PMID:Ganglioneuroblastoma presenting as myasthenia gravis. 86 63

Immunohistochemical studies have shown that almost all thymomas of myasthenia gravis patients contain at least one protein sharing an antigenic determinant with the nicotinic acetylcholine receptor (AchR) of human muscle. We describe the characterization of this protein (p153) which has a molecular weight of 153 and an isoelectric point of 5.0. By treatment of p153 with endoglycosidases, no significant glycosylation has been detected. Immunologically, p153 crossreacts with monoclonal antibodies against the amino acid sequence 371-378 of the alpha-chain of the AchR. No cross-reactivity to the main immunogenic region of the AchR nor an alpha-bungarotoxin binding site are found. By Western blotting, p153 was generally neither detectable in normal tissues nor extrathymic tumors with the exception of paraganglioma and neuroblastoma. In conclusion, the structure of p153 is apparently unrelated to the AchR from muscle or the alpha-bungarotoxin binding proteins from thymoma. Since there is no evidence for an AchR expression in thymoma, the antigenic homology of p153 with the nicotinic AchR might be relevant for triggering an intrathymomatous autosensitization of maturing T cells and could be responsible for the high association of thymomas with myasthenia gravis.
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PMID:Characterization of a protein with an acetylcholine receptor epitope from myasthenia gravis-associated thymomas. 215 8

Antibodies reacting with human neuroblastoma cells (NBL) are distinct from the "classical" anti-acetylcholine receptor (AChR) antibodies in myasthenia gravis (MG). The influence of therapeutic interventions on serum anti-NBL antibody levels was followed in 42 MG patients. Thymectomy alone was performed in 28 patients while immunosuppressive medication was given to 14 patients out of whom 10 also had a thymectomy. In most patients serum anti-NBL antibody titers declined after thymectomy and/or during immunosuppressive treatment, though individual variations in the antibody response could be observed. Sequential examinations of individual patients revealed an association between the clinical severity of MG and anti-NBL antibody levels. No correlation between the treatment-induced changes of anti-NBL and anti-acetylcholine receptor (AChR) antibody titers could be observed during the follow-up period in MG patients positive for both types of antibodies. These findings further emphasize the immunological complexity of MG. Anti-NBL antibodies represent a pathogenic marker of the disease and display a regulation different from that of the anti-AChR antibodies.
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PMID:Effect of thymectomy and immunosuppressive therapy on anti-neuroblastoma antibody levels in patients with myasthenia gravis. 206 57

Serum autoantibodies found by radioimmunoassay in 27 of 52 patients with the Lambert-Eaton myasthenic syndrome (LES) bound specifically to a soluble omega-conotoxin binding component of a voltage-gated Ca2+ channel (VGCC) complex extracted from small cell lung carcinoma (SCC). These antibodies were not found in 43 control patients with other neurologic diseases, including myasthenia gravis, peripheral neuropathies, and amyotrophic lateral sclerosis, or in 9 patients with endocrine autoimmunity, but they were found in 2 of 21 control patients with SCC without a history of LES, 1 of whom had severe autonomic neuropathy. Seropositivity was more frequent in patients with LES who had evidence of a primary lung cancer (76%) than in those with other neoplasms or without evidence of cancer (30%). Antigens extracted from SCC tumor lines derived from patients with and without LES and from a human neuroblastoma line yielded results that were highly correlated. A control extract of colonic carcinoma (derived from a patient with LES) yielded negative results. The data implicate a tumor-associated VGCC as the autoimmunizing stimulus in a subset of patients with LES and provide the first direct evidence that the VGCC complex in SCC is a target for some LES antibodies. The serologic test described should be a useful aid in diagnosing LES.
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PMID:Autoantibodies bind solubilized calcium channel-omega-conotoxin complexes from small cell lung carcinoma: a diagnostic aid for Lambert-Eaton myasthenic syndrome. 255 95

Forty-four of 109 myasthenia gravis (MG) patients (40%) had serum antibodies against human neuroblastoma cells (NBL). Anti-NBL antibodies were most frequent in the sera of MG patients who had either a hyperplastic thymus or a thymoma, clinically mild to moderately severe generalized MG, and a long disease duration (greater than or equal to 11 years). No correlation between individual anti-NBL antibody and anti-acetylcholine receptor (AChR) antibody titers was observed. Seven of the 19 patients negative for anti-AChR antibodies (37%) had anti-NBL antibodies in their sera. These findings provide further evidence for immunological heterogeneity in MG. In addition to the typical autoantibodies to the AChR, autoimmunization against neural antigens can frequently be detected in these patients.
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PMID:Anti-neuroblastoma antibodies in myasthenia gravis: clinical and immunological correlations. 259 87

Rhabdomyosarcoma (RMS), a common soft tissue tumor in children, may often be difficult to distinguish from Ewing's sarcoma, neuroblastoma, and malignant lymphomas. Confirmation of the skeletal muscle origin of RMS depends partly on the demonstration of striations in tumor cells that are usually undetectable in poorly differentiated tumors. A number of tissue markers (e.g., myoglobin and desmin) are currently being used to establish the origin of RMS. However, most of these markers lack specificity and have relatively low sensitivity. We have investigated the specificity and sensitivity of anti-skeletal muscle antibody (ASMA) from patients with myasthenia gravis in the diagnosis of childhood RMS. Out of eight cases of childhood RMS (four embryonal and four alveolar) examined, two showed striations with hematoxylin and eosin and four with phosphotungstic acid hematoxylin. Myoglobin was detected in five tumors; only well-differentiated tumor cells contained myoglobin. Anti-desmin antibody and ASMA reacted with cells in all the eight tumors whether or not the tumor cells were well differentiated. Anti-skeletal muscle antibody did not react with nine lymphomas, four Ewing's sarcomas, four neuroblastomas, four osteogenic sarcomas, four lipomas, eight duct carcinomas of the breast, and eight squamous cell carcinomas of the lung. Eight leiomyomas and four leiomyosarcomas of the uterus were compared for their reactivity with anti-desmin antibody and ASMA. All the tumors stained with anti-desmin antibody and none with ASMA. The results show that ASMA is useful in the diagnosis of childhood RMS and is a more sensitive reagent than anti-myoglobin antibody. Unlike anti-desmin antibody, it can distinguish skeletal muscle tumors from smooth muscle tumors.
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PMID:Use of anti-skeletal muscle antibody from myasthenic patients in the diagnosis of childhood rhabdomyosarcomas. 355 41

The autoimmune nature of acquired myasthenia gravis is well documented. Although anti-acetylcholine receptor antibodies are pathognomonic for this disease, their significance in the immunopathogenesis of myasthenia gravis may differ among patients. The presence of antibodies against human neuroblastoma cells in myasthenic sera was studied using the 125I-labelled protein-A radioimmunoassay and indirect immunofluorescence. For comparison sera of patients with other neurological diseases were examined. Significant levels of antibodies against neuroblastoma cells were found in the sera of over 60% of myasthenia gravis patients and in some patients of the other disease groups, but mainly in lower titers. Our findings suggests a more generalized neuroimmunological abnormality in some myasthenia gravis patients.
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PMID:Antibodies against human neuroblastoma cells in the sera of patients with myasthenia gravis. 621 Mar 5

Patients with myasthenia gravis (MG) have antibodies to the muscle nicotinic acetylcholine receptor (mAChR) which are responsible for their muscle weakness: but some patients with MG and other neuroimmunological disorders have autonomic symptoms. We characterised the neuronal forms of AChRs (nAChRs) into two neuroblastoma cell lines and developed immunoprecipitation assays to test for antibodies to the alpha7- and alpha3-containing nAChR subtypes, present in the autonomic ganglia. We then tested 70 sera samples from MG patients, 38 from subjects with other neurological diseases, and 30 from healthy individuals, for antibodies to these two forms of neuronal AChR subtypes. We used the alpha7 subtype extracted from the human neuroblastoma IMR32 cell line labeled with 125IalphaBungarotoxin (alphaBgtx), and the alpha3-containing subtype extracted from the human neuroblastoma SY5Y cell line labeled with 3H-Epibatidine (Epi). Nine subjects (five MG, one GBS, one CIPD and two LEMS) were positive for the alpha7 subtype; and four for the alpha3-containing subtype (two MG patients, one LEMS and the same GBS patient). None of the MG patients with undetectable levels of antibodies against muscle AChR were positive. The patients with serum antibodies to alpha7 or alpha3-containing neuronal AChRs showed a range of clinical features including autonomic symptoms and thymoma in two MG patients. These results indicate that patients with MG and other immune-mediated disorders can have antibodies to neuronal AChRs, and that these may contribute to the clinical characteristics of the diseases.
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PMID:Antibodies against neuronal nicotinic receptor subtypes in neurological disorders. 1062 72

Nicotinic acetylcholine receptors (AChRs) are ligand-gated cation channels that are present throughout the nervous system. The muscle AChR mediates transmission at the neuromuscular junction; antibodies against the muscle AChR are the cause of myasthenia gravis. There are numerous subtypes of AChRs present throughout the nervous system. These neuronal AChRs are closely related to the muscle AChR structurally, but are pharmacologically and immunologically distinct. The ganglionic (alpha3-type) neuronal AChR mediates fast synaptic transmission in sympathetic, parasympathetic, and enteric autonomic ganglia. Ganglionic AChR antibodies are found in up to 50% of patients with autoimmune autonomic ganglionopathy (AAG). Patients with AAG present with severe autonomic failure. Major clinical features include orthostatic hypotension, gastrointestinal dysmotility, anhidrosis, bladder dysfunction, and sicca symptoms. Impaired pupillary light reflex is often seen. Like myasthenia, AAG is an antibody-mediated neurological disorder. Patients may improve with plasma exchange treatment or other immunomodulatory treatment. Experimental AAG, which recapitulates many of the features of the human disease, can be induced in rabbits by immunization against the ganglionic AChR or by passive transfer of antibodies to mice. Ganglionic AChR IgG inhibits nicotinic membrane current in cultured neuroblastoma cells. Central nervous system neuronal AChRs may also be targets of autoimmunity. For example, antibodies against alpha7-type AChRs have been identified in a few patients with encephalitis. It is still unclear if antibodies against receptors in the central nervous system can directly cause disease.
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PMID:Neuronal acetylcholine receptor autoimmunity. 1856 61

Acetylcholine (ACh) is the neurotransmitter used by cholinergic neurons at the neuromuscular junction, in parasympathetic peripheral nerve terminals, and in important memory-related circuits in the brain, and takes part in other critical functions. ACh is synthesized from choline and acetyl coenzyme A by the enzyme choline acetyltransferase (ChAT). The formation of ACh in cholinergic nerve terminals requires the transport of choline into cells from the extracellular space and the activity of ChAT. High-affinity choline uptake (HACU) represents the majority of choline uptake into the nerve terminal and is the acutely regulated, rate-limiting step in ACh synthesis. HACU can be differentiated from nonspecific choline uptake by inhibition of the choline transporter with hemicholinium. Several methods have been described previously to measure HACU and ChAT activity simultaneously in synaptosomes, but a well-documented protocol for cultured cells is lacking. We describe a procedure for simultaneous measurement of HACU and ChAT in cultured cells by simple radionuclide-based techniques. Using this procedure, we have quantitatively determined HACU and ChAT activity in cholinergically differentiated human neuroblastoma (SK-N-SH) cells. These simple methods can be used for neurochemical and drug discovery studies relevant to several disorders, including Alzheimer's disease, myasthenia gravis, and cardiovascular disease.
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PMID:High-affinity choline uptake (HACU) and choline acetyltransferase (ChAT) activity in neuronal cultures for mechanistic and drug discovery studies. 2275 95


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